Analysis of saliva and other oral fluids has great potential in diagnosis of oral and systemic diseases, in monitoring levels of environmental toxins and drugs-of-abuse, and in preliminary screening for exposure to biological and chemical warfare reagents, The use of saliva and other oral fluids as diagnostic samples may be preferred in many applications over other bodily fluids because of the ability for fast and inexpensive sampling in clinical as well as non-clinical settings. Although, clinical studies have demonstrated usefulness of saliva and other oral fluids in some applications for detection of markers of oral and systemic diseases, the development of diagnostic technology and devices has not met the expectations. Moreover, the current assay techniques are time-consuming, require relatively large amounts of samples and are not amenable to automation and portability. The objectives of this application are the following: 1) Development of an integrated microfluidic system for simultaneous multi-analyte detection in saliva and other oral fluids. The prototype will be capable of rapid and sensitive analysis of minute sample volumes and will attain higher selectivity by performing multiplexed analysis; 2) Analysis of mediators of oral and periodontal diseases found in oral fluids (i.e., P. gingivalis endotoxin, interleukins, and bone breakdown fragments) using the proposed bench scale prototype; and 3) Validation of the technology in a longitudinal human trial of patients at low and high risk for the development of periodontal diseases. Success of these objectives should provide for technology transfer and utilization of this device in clinical periodontology as well as potential applications in preliminary screening for systemic diseases and exposure to biological warfare agents.